19B18: Exam Report
Compare and contrast the pharmacology of metaraminol and noradrenaline.
71% of candidates passed this question.
Marks were distributed across pharmaceutics, uses, dose & administration, mechanism of action, Pharmacokinetcs and Pharmacodynamics. Common omissions were doses/rates of infusion, effects other than on heart/SVR (e.g. splanchnic, renal blood flow), indirect effect of metaraminol, receptor effect of noradrenaline other than alpha 1 and tachyphylaxis.
G7i / 19B18: Compare and contrast the pharmacology of metaraminol and noradrenaline
Metaraminol
Noradrenaline
Chemical
Metaraminol
synthetic non-catecholamine with direct & indirect sympathomimetic effects but predominant α-adrenoreceptor activity
Noradrenaline
Endogenous catecholamine neurotransmitter released from postganglionic sympathetic n. endings
Also accounts for 20% adrenal medulla secretions
Use
Metaraminol
hypotension
Noradrenaline
to ↑SVR
Presentation
Metaraminol
clear solution 10mg/mL
Noradrenaline
Clear, colourless solution 1mg/mL
Brown ampoule → prevent light oxidation
Must be diluted in D5W to provide sufficient acidity to prevent oxidation
1 pH D5W = 4, pH 0.9% NaCl = 6
Metaraminol commonly comes in pre-formed syringes 0.5mg/ml
Dose
Metaraminol
0.5 – 1mg bolus or as an infusion 1 – 10mg/hr
Noradrenaline
Infusion 1 – 20mcg/min
Metaraminol used during intubation and sedation procedures, easy to administer peripherally
Route
Metaraminol
IV
Noradrenaline
central vein
Obvious advantage of peripheral administration w M
Onset
Metaraminol
1-2mins
Noradrenaline
immediate: tachyphylaxis with prolonged infusions
Both confer tachyphylaxis
MoA
Metaraminol
Indirect: taken up by postganglionic symp. nerve endings
Displaces NA
NA released
Mostly affects α1 adrenoreceptors
α1 → Gq → stimulates Phospholipase C → ↑IP3 & DAG → open Ca2+ channel → VC of smooth m. of vessels
Direct
CVS – ↑SVR
Regional BF – ↓CBF & ↓renal BF
Noradrenaline
α1 = α2 > β1 > β2
Potent α agonist
Equal β1 cf. adrenaline
Little β2 activity
α1 → Gq → stimulates Phospholipase C → ↑IP3 & DAG → ↑Ca2+
Smooth m. vasoconstriction
Cardiac: weak +ve inotropy
Metabolic: ↑BSL
α2 → Gi → inhibits AC → ↓cAMP → ↓Ca2+
CNS: ↓symp. outflow
Peripheries: inhibits NA release from nerve terminals
Platelets: ↓plat. aggregation
β1 → GS → ↑AC →↑cAMP → ↑Ca2+
Heart: +ve inotropy, +ve chronotropy, +ve dromotropy
Renal: ↑renin, ↑AII
Metabolic: ↑lipolysis, ↑FFAs
PD
Metaraminol
CVS – increased SBP & DBP, reflex bradycardia, increase CA blood flow
Noradrenaline
CVS
Intense VC all vascular beds = ↑↑SVR
↑HR
↑FoC
Reflex ↓HR
Renal, hepatic, cerebral & skeletal m. BF all ↓
RESP
Small ↑MV
METABOLIC
↑BSL
↑FFA
RENAL
↑Renin
PK
Metaraminol
A
(limited data)
D
doesn’t cross BBB. 45% PPB
M
not a MAO/COMT substitute
E
Noradrenaline
A
IV administration
D
25% uptake via 1 lung passage
M
rapid metabolism t½ = 2 mins
MAO/COMT pathway
E
metabolites conjugated to glucuronic acid for renal excretion
Adverse Effects
Metaraminol
Reflex ↓HR
Headache
Dizziness
Tremor
Nausea &vomiting
LV failure
Noradrenaline
Extravasation → necrosis
Headache
Anxiety
NB CAUTION: Patients taking MAO inhibitors
PREGNANCY = ↑contraction of pregnant uterus, foetal bradycardia & asphyxia